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Thyroid hormone direct repeat 4 response element is a positive regulatory element for the human TR2 orphan receptor, a member of steroid receptor superfamily

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Abstract

We demonstrate that TR2 orphan receptor (TR2) may induce transactivation activities via an AGGTCA-like-direct-repeat-4 consensus thyroid hormone response element (DR4-TRE) system. TR2 showed a slightly greater binding affinity than thyroid hormone receptor α1 (TRα1)/retinoid X receptor α (RXRα) heterodimer with Kds 0.5 nM and 2.3 nM, respectively. These receptors, TR2 and TRα1/RXRα heterodimer, competed with each other on binding to limited amounts of DR4-TRE. TR2 canceled the suppression effect of unliganded-TRα1 on CAT reporter activity in a dose-dependent fashion. Estrogen receptor (ER) and 2P2 (a mutated TR2 with P box sequence of androgen receptor) failed not only to bind to DR4-TRE but also to recover this inhibitory effect of unliganded TRα1. However, when T3 was supplemented, estradiol-ER competed for a full CAT activity while TR2 showed an additive effect on the transcriptional activation. These results indicate that DNA binding is essential for TR2 to take action and fully functional liganded TRa1 may rely on common factors shared with ER but not TR2.

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  1. Departments of Pathology, Biochemistry, Urology, and Cancer Center, University of Rochester, George Whipple Laboratory for Cancer Research, Rochester, NY, USA

    Chawnshang Chang & Huei-Ju Pan

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  1. Chawnshang Chang
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  2. Huei-Ju Pan
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Chang, C., Pan, HJ. Thyroid hormone direct repeat 4 response element is a positive regulatory element for the human TR2 orphan receptor, a member of steroid receptor superfamily. Mol Cell Biochem 189, 195–200 (1998). https://doi.org/10.1023/A:1006918402474

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